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From ancient times, immortal sages and healers have developed and used safe, effective medicines to treat human ailments using the bounty of the flora around them. Today approximately 60% of the world’s population still depends almost entirely on plants for their medications.

Yet here in our modern western society we depend on pharmaceutical offerings where only 25 to 50% of the medications are derived from plants.

Educated patients demanded action. Western medicine took notice. Today, medical scientists mine those same fields used by the traditional healers in search of the ingredients that provided these age-old proven remedies their longevity over the centuries. Those of us who inhabit modern society are now faced with a pivotal question:
Should these ancient natural remedies be subject to the same rigorous, costly, time consuming research constraints established for synthetic medical treatments? How will that path impact our ability to access these ancient remedies? How does the fact that no patent can be made for a product of nature play into this scenario? Our society needs to have a serious discussion on our current entangled drug approval process – specifically on our healthcare costs and outcomes. One thing we can all agree on is: costs play a key role in health outcomes.

Scientists move much more quickly than the institutions we’ve create to manage our complex by society. In their quest to explore the botanical world for remedies to human ailments scientists have found a specific category of phytochemicals produced by plants, called “secondary metabolites” that hold promising health applications. Nature offers an immense variety of secondary metabolites, such as tannins, terpenoids, alkaloids, and flavonoids.

Just as your body metabolizes nutrients in your body to produce other bio-chemicals (e.g. hormones) so does a plant. Secondary metabolites are not technically essential to a plant’s ability to live – but they do play a critical role in keeping all the plant’s systems working effectively and in some cases its ability to survive extinction. They often provide a plant with natural defenses against hungry herbivores and insects, as well as lethal pathogens.

Anatabloc’s key ingredient is a secondary metabolite named anatabine. It’s a naturally occurring phytochemical found in various plants in the Solanaceae plant family. (This wide selection of seed producing, flowering plants, is considered the “potato” family. There are 42 genera of plants in it. U.S. Department of Agriculture.)

Its molecular formula is C10H12N2. For us non-science majors that’s a combination of carbon, hydrogen, and nitrogen atoms. The nitrogen puts anatabine in the alkaloid family.

There are thousands of known plant alkaloids (and many as yet still unknown) and their individual chemical structures vary greatly. At this time it’s still difficult to determine the precise role of each known plant alkaloid. Currently they are considered some of the most promising bioactive components in the plant kingdom, and as such, serve as a rich reservoir for possible applications to improve human health.

There are many plant alkaloids currently available for consumer purchase as nutritional dietary supplements. These include but are limited to: vincamine ( Vinpocetine), huperzine, berberine, aziridine ( Ayervedic Hymalayan Yew), peperine (found in black pepper) and quinine ( in tonic water.) Probably the most popular plant alkaloid is caffeine.

Still there are some plant alkaloids that are sold to the public that perhaps shouldn’t be, – we’re looking at you nicotine. But nicotine is not alone in this category. Various Chinese medicinal herbs, now easily obtainable, contain the alkaloid pyrrolizidine and there’s valid reason to question the safety for human consumption of these Chinese medicinal herbs – especially over a long period.

And no discussion of alkaloids would be complete without mentioning that among them are some of the most toxic and/or dangerous phytochemicals in the plant kingdom. Opiate, cocaine, and coniine among them.

The important thing to note about anatabine is that it has been consumed for centuries in vegetables such as eggplants, green tomatoes, peppers and especially in tobacco products. And for a great many of those years its intense consumption in tobacco was widespread.

There’s an overwhelming amount of research on the toxic effects of the elements contained in tobacco. After extensive (days, if not weeks) of review of these studies, I failed to find any research to substantiate any claim that the anatabine in the tobacco played a role in the toxic effects of tobacco consumption. Yes, tobacco contains phytochemicals whose consumption (especially smoking consumption) have been proven to cause serious and sometimes deadly human health disease – but anatabine is not in this group. Chlorophyll is also a phytochemical in tobacco – do we consider that toxic to humans?

Tobacco consumption (and the plethora of research on it) allows us to gage the impact of large doses of anatabine on humans. Just how much anatabine was consumed from tobacco products compared to a therapeutic dose of anatabine found in Anatabloc?

Marlboro, the most common US cigarette contains .55 mg of anatabine in one “rod filler” of tobacco. A rod filler, is the cigarette without the filter and usually contains 1 gram of tobacco rolled in paper.

Smokeless tobacco consumers (chewing tobacco and snuff) have the greatest exposure to anatabine. Consumption levels of smokeless tobacco vary more widely among users than that of cigarettes. But numerous sources report a typical level of consumption is 12 grams of moist snuff a day. Using Copenhagen as the most common snuff brand with an anatabine content of 1.4mg/gram dry weight and moisture content of 50%, their average consumption of anatabine stands at 16.8mg/ day.

Intake of anatabine from food sources, such as tomatoes, eggplants, and red peppers would be much lower than the amounts consumed in tobacco use.

Based on these data, the smokeless tobacco consumer ingests the highest level of anatabine, at 16.8 mg/day. The cigarette smokers take in anywhere from 2 to 20mg/day, depending on their cigarette consumption. The therapeutic dose of Anatabloc is 8 mg/day.

Way before it was sold to the public, the original manufacturer of Anatabloc, Star Scientific, did numerous, high quality “toxicology” studies on anatabine. These are specific tests to determine if a substance is dangerous, and if so at what level, to humans. Studies were initially done on mice, rats and rabbits. The animals in these studies were given doses much greater (10x) than the average human dose of 8mg / day. These tests failed to show any physical danger in the consumption of anatabine – even doses far beyond those recommended.

Additional studies were done to determine if anatabine had any potential to harm a fetus in utero and to see if taking it could causes changes to human DNA. The latter is a “genotoxicity” study – changes cell DNA is instrumental in the genesis of cancer. (A genotoxicity study is done under a microscope.) Again, these tests failed to provide any evidence of danger at even doses well beyond those recommended.

Still not satisfied, a study was done to determine what, if any, potential anatabine might have for abuse. This means they set out to see if it’s addictive. These studies are called, “behavioral toxicology” studies. The conclusion of the researchers at the end of these studies is that anatabine did not create addiction. Animals given steady doses of it failed to demonstrate any signs of addiction (like nicotine or alcohol) or aroused (like a stimulant or psychotic) that would indicate a potential to be abused by humans.

Now you might say – “Well these studies were funded by the manufacturer, of course they’re going to have results that are favorable to the product.” It’s a good point, but not applicable in the development of anatabine for sale to the public. The manufacturer’s risk of liability lawsuits depends on the accuracy of these tests. Say what you may about the Trail Lawyers Association – liability lawsuits instill, to our benefit, some proper fear in the makers of any dietary supplement, topically applied or ingested product.

The human studies of anatabine as a supplement were conducted after those above confirmed its basic safety. These clinical studies set out to determine if anatabine could help people to quit smoking. The hope was that anatabine would satisfy a cigarette smoker’s craving for nicotine. Because anatabine is not addictive this was considered an ideal way to a help people break their addiction to cigarettes.

The initial studies involved 403 participants. In these studies only nine reports of unpleasant side-effects were reported. (In pharmaceutical research, even mild to moderately unpleasant side-effects are called “Adverse Events.”)

One study involved 106 heavy smokers, among whom 80% were overweight or obese. Participants were asked to take Anatabloc 3x/day for a total intake of 6mg a day. From this study scientists concluded that 10 (10%) of the participants reported mild to moderate unpleasant side-effects (adverse events) that were most likely related to their consumption of anatabine. The most common complaint involved gastrointestinal intolerance related to the mint flavoring or the mannitol (a natural sugar substitute) used in the lozenges. Only one subject dropped out of the study, this was due to an allergic reaction (skin rash).

The interesting revelation from this last study was that people who were taking the appropriate doses of Anatabloc to relieve their cravings for nicotine – had 30% lower levels of hsCRP in their blood as compared to the people who were not taking the anatabine supplement. The level of C-reactive protein (CRP) in the blood tells you the amount of inflammation that’s found your body. A high-sensitivity CRP test, (hs-CRP,) can help determine your risk of a heart attack and stroke.

Let me point out that those who saw their hsCRP levels reduced by 30% were heavy smokers, who were still smoking heavily when their hs-CRPs went down – while taking Anatabloc.

The Roskamp Institute, based in Sarasota Florida, is highly esteemed in the medical research community. It attracts world-class scientists to its facilities on the west coast of Florida. Its mission is to develop safe and effective new drug therapies to successfully treat diseases of the mind and to promote healthy aging. It does this through both high-quality research and clinical services. Its primary focus is on the treatment and eventual cure for Alzheimer’s disorder.

The scientists at Roskamp were sufficiently intrigued by what had been learned about anatabine before it arrived at their facility to give it a go on the mice. More than just seeing it reduce hsCRP blood levels – they wanted to know how it did this at the molecular level.

What they found was that anatabine in the human body mimics the body’s most common neurotransmitter, acetylcholine (a-cee-till-koe-leen.) In the body acetylcholine seeks out and links-up with “cholinergic receptors.” When anatabine pairs with cholinergic receptors – this new molecule blocks certain neuro-chemical actions that lead to inflammation.

To understand why anatabine worked so well with my daughter Rosie, who suffers with autism, it helped to know that it’s molecular size is very small. Remember the C10H12N2 composition? This is a very small molecule – its weight is 160.22 g/mol. (By comparison the molecular weight of curcumin is 368.38 g/mol; quercetin is 302.24 g/mol; and Omega-3 fatty acids weigh in at a hefty 909.37 g/mol)

The tiny molecule size helps anatabine pass through the blood-brain barriers more easily than most any other natural anti-inflammatory. And it does so without all the unpleasant and sometimes dangerous side-effects of the NSAID “non-steroidal anti-inflammatory drugs” and anti-inflammatory steroid drugs currently available either over-the-counter or by prescription.

That said, it doesn’t mean it’s going to work for everyone. There are different types of inflammation caused by different mechanisms in the body. But for those of us who have found it to bring relief – there is at this time no other substitute.

Let me state here, right up front: The FDA found no clear human safety issues with the consumption of Anatabloc.

One of the reasons it’s taken so long to get this website up is the amount of effort I put into investigating every, single safety aspect. Any hint, innuendo, and or suspicion of danger stemming from the human consumption of the alkaloid anatabine lead me on a chase to confirm it. And doing this research with no help from the science team behind Anatabloc made it especially time consuming.

The FDA did not ban the sale of Anatabloc. The beleaguered company behind it; initially Star Scientific, and then Rock Creek Pharmaceutical decided, on their own, to suspend sales of their dietary supplement. Yes, the FDA had issued warnings to the company, but we’ll get to the details of those issues further on. You’ll see they had nothing to do with the human safety of the supplement. You need to know it takes money – lots of money, to deal with the FDA. This includes FDA “User Fees” and outside legal fees. And, in August 2014 money was in short supply at Rock Creek Pharmaceutical.

The company had operated in the red for 11 years. In 2013 it reported a loss of $33.1 million from continuing operations and revenues of only $9.1million.

In December 2013 Star Scientific underwent a transition that placed Anatabloc under the direction of its subsidiary, Rock Creek Pharmaceutical. The management and leadership of Rock Creek were medical scientists with professional roots deep in research and development of pharmaceutical compounds to cure human disease. Therefore, as part of this transition, the corporate focus went from dietary supplements to pharmaceutical drug development.

For the six months that ended on June 30, 2014, Star Scientific/Rock Creek Pharmaceutical posted a net loss of $22.5 million.

In a regulatory filing Rock Creek Pharmaceuticals said it made the decision to suspend sales in August 2014 after a review of how its dietary supplement business would affect its main focus: the development of pharmaceutical products.

Warning Letter December 24, 2013

Let’s be fair, the FDA is itself a beleaguered operation.

This single agency is responsible for a vast range of products central to the health and daily well being of every living American. They ensure the safety and effectiveness of two trillion dollars worth of products a year. This includes everything from food and cosmetics to drugs, and medical devices such as artificial hearts, surgical lasers, and gene therapy. It reaches to livestock and agricultural products; including pesticides, genetically engineered foods, cloned animals and nanotechnology products.

And they do this in an ever-increasing atmosphere of cost containment, budget slashing and hostility. Granted with a budget of over $4 billion, it’s hard to have sympathy for their money problems. Perhaps too, there’s a vast number of changes that could allow this behemoth of an agency to operate more efficiently and effectively – but no one can say they have an easy job.

I’m taking on this petition effort with deep faith in the integrity and intelligence of the people who work at the FDA. Each day they carry out the critical mandate of ensuring our safety.

The dietary supplement industry itself is a $30 billion business and growing. In 1994 Congress passed the Dietary Supplement Health and Education Act (DSHEA.) This law provides the framework for assuring the safety of dietary supplements and ingredients. It sets guidelines for labeling, use of claims and nutritional support statements, and establishes other criteria unique to dietary supplements and ingredients.

This legislation firmly placed dietary supplements in the realm of foods rather than drugs. Under DSHEA, the company making and distributing a dietary supplement is responsible for determining its human safety. The company is further responsible for the accuracy of any representations or claims made about the supplement. Claims must substantiated by adequate evidence to show that they are not false or misleading.

This means that dietary supplements do not need approval from the FDA before they are sold to the public. Except in the case of a new dietary ingredient, where pre-market review for safety data and other information is required by law, a company does not have to provide the FDA with the evidence it relies on to substantiate safety or effectiveness claims before or after it places its product on the market.

Once they are placed on the market the responsibility is on the public to alert the FDA of possible illegal acts in the dietary supplement industry.

In late August 2012 the FDA claimed to be acting on a tip from the Department of Defense regarding dietary supplements being marketed with claims of curing or treating concussions and/or Traumatic Brain Injury (TBI) when it issued Warning Letters to two supplement makers, PruText Rx of Highlands Ranch, CO and the Trinity Sports Group of Plano, TX. These companies were marketing products expressly for the treatment of these serious neurological injuries.

Later, in December of 2013, claiming to be acting on the same concern, the FDA issued a warning letter to Star Scientific the maker of Anatabloc.

“Because you failed to do ‘X’ you fell into category ‘Z’ which requires a new application called “I” to filled out and submitted to Office A (for a small fee.)”

The DSHEA laws designated dietary supplements to be regulated as foods, to supplement but not replace, food in the human diet. With this in mind, DSHEA was designed so that makers of drugs – arguably more dangerous substances in the minds of many compared to a dietary supplement – wouldn’t be allowed to slip through the rigorous (and costly) safety tests required for their introduction to the consumer market place. DSHEA specifically prohibits dietary supplement makers from using “disease claims” to promote their products. Every dietary supplement company needs to know that as stated in DSHEA:

“Diagnose, cure, treat or prevent” – I understand. But “mitigate”? According to the New Oxford American Dictionary the definition of “mitigate” is: (verb) to make less severe, serious or painful? What this basically means is that a dietary supplement maker cannot mention by name any disease or disorder in their promotional and packaging materials, unless there is scientific evidence the FDA deems acceptable to allow these claims. That’s why a supplement will state, “improves mood” and not “alleviates depression.”

Even if the ingredients aren’t harmful, the FDA goes beyond it mandate to protect consumers from fraud by stating its intention here is to make certain Americans seek proper medical treatment, and not try to self-diagnose, or worse fail to take precautions to heal properly.

Once a supplement maker is caught making drug claims the FDA quickly moves on to citing them for misbranding their product. A disease “is not amenable to self-diagnosis and treatment by individuals who are not medical practitioners; therefore, adequate directions for use cannot be written so that a layperson can use these (now found by the FDA to be) “drugs” safely for their intended purposes.”

If that makes you worry about “Big Government” and the “Nanny State” it should. Was this “intention” created when medical professionals were easily accessible and affordable to everyone? How does the FDA decide if a disease is amenable or not to self-diagnosis? What if it’s a disorder (autism) and not a disease? Is it safe to ask how many “qualified medical professionals” out there will suggest a dietary supplement rather than a prescription drug, when they’re constantly courted by pharmaceutical reps?

There is some relief to be found in this difficult situation. In a significant case against the FDA , the U.S. Court of Appeals, District of Columbia 164 F3d 650 Pearson v. Shalala ruled in 1999 ,

“But all the government offers in support (of this issue of misbranded labeling) is the FDA’s pronouncement that ‘consumers would be considerably confused by a multitude of claims with differing degrees of reliability.’ 59 Fed. Reg at 405. Although the government may have more leeway in choosing suppression over disclosure as a response to the problem of consumer confusion where the product affect health, it must still meet its burden of justifying a restriction of speech – here the FDA’s conclusory assertion falls far short. See Ibanez 512 U.S. at 146 s. Ct 2084 (‘If the protections afforded commercial speech are to retain their force, we cannot allow rote invocation of the words, ‘potentially misleading’ to supplement the [government’s] burden to demonstrate that the harms it recites are real and that its restrictions will in fact alleviate them to a material degree.’) Edenfield, 507 U.S. at 771, 113 S. Ct. 1792 (invalidating a ban on in-person solicitations by accountants where the government failed to present ‘studies’ or ‘anecdotal evidence’ showing that such a solicitation posed a danger of fraud, overreaching, or compromised independence.”

The court in this case ruled to provide support to a supplement manufacturers ability to make claims – but it takes money to take the FDA to court.

For Anatabloc, at this point, the law is the law, and DSHEA is DSHEA. Mistakes were most definitely made on the part of Star Scientific. On this issue of “unauthorized drug claims” the other two dietary supplement makers singled out in this issue of concussion/TBI claims, as well as Star Scientific, removed any statements that indicated their product was a drug (could be used to diagnose, treat etc.) from their websites and promotional materials. The other two dietary supplement makers continue to sell their products.

The New Dietary Ingredient Issue

As for Anatabloc, the unlawful “drug claims,” were just the beginning. The FDA threw the book at them.

A critical point of the FDA’s contentions against Star Scientific / Anatabloc was that it had failed to file a New Dietary Ingredient (NDI) notification for anatabine as a dietary ingredient.

For the lay-person, a “New Dietary Ingredient” is basically a new substance that has never before been consumed by humans. A substance, according to the FDA website :

Question: Is a NDI Notification required for a dietary supplement containing a NDI if the supplement contains only dietary ingredients that have been present in the food supply as articles used for food in a form in which the food has not been chemically altered?

Answer:No. Even though an ingredient that was used to make a conventional food before October 15, 1994 is a NDI (unless it was also marketed as a dietary ingredient before that date), a NDI notification is not required for a dietary supplement containing the NDI as long as the supplement contains only dietary ingredients that have been present in the food supply as articles used for food in a form in which the food has not been chemically altered (21 U.S.C. 350b(a)(1)).

As stated in the Science portion of this Learn More section, anatabine has been in the food supply for as long as humans have been eating cauliflower, potatoes, tomatoes, and eggplants.

This fact allows anatabine to satisfy the criteria to be a dietary ingredient that has been in the food supply. Further, the “anatabine citrate” found in Anatabloc is created by the salt used to extract the bio-molecule out of the plants, the molecular structure of anatabine remains intact and has not been “chemically altered.” It’s similar to the Ester-C version of Vitamin C, where calcium has been added to allow easier absorption.

In their December 2012 Warning letter the FDA insists, “The FDA is not aware of any information indicating that anatabine itself is an article used for food.” (For those of not dealing with legal issues with the FDA for a living: I’ve come to conclude that when the word “article” appears here it’s best for us non-legal types to substitute, “substance.”) But if we follow the FDA’s logic on this, can anyone remember when Omega 3 fatty acids ALA, EPA and DHA were used as “articles of food” after they were extracted from their sources? How about Same? Silymarin? Anthocyanins?

Again, from the FDA website, DSHEA established that a dietary ingredient is:

“a vitamin; a mineral; an herb or other botanical; an amino acid; a dietary substance for use by man to supplement the diet by increasing total dietary intake; or a concentrate, metabolite, constituent, extract, or combination of any of the above dietary ingredients.

From the Science page of the Learn More section, you’ll see how it’s an established fact that anatabine is a metabolite.

This single issue of the status of anatabine being a “new dietary ingredient” versus an “article” (substance) present in the food supply and being sold in a non-chemically altered state” is pivotal to Rock Creek Pharmaceuticals ability to legally sell Anatabloc across state lines in the U.S.

The Investigational New Drug Issue

The FDA threw the book at Star Scientific. And it wouldn’t be a book without chapters. Here’s the next:

An unconnected provision of DSHEA states “an ingredient may not be marketed as a dietary supplement if the article has been authorized for ‘investigation as a new drug’… for which substantial clinical investigations have been instituted and for which the existence of such investigations has been made public.” 21 USC §321(ff)(3)(B)(ii). In other words, once the ingredient is seriously investigated as a drug, it can’t be used in a dietary supplement unless it was marketed as the supplement first.

Here’s how the events played out: the FDA acknowledged the company began selling products containing anatabine in 2010. Star Scientific/Rock Creek believed (and still does) that anatabine did not qualify as a New Dietary Ingredient, so it did not file an NDI notice for the ingredient. It is also undisputed that the Roskamp Institute filed an Investigational New Drug (IND) application for anatabine in 2012.

A dietary ingredient that has been present in the food supply and safely consumed by humans can be sold as a supplement. Later if it’s found that the substance has potential as a drug, a pharmaceutical maker files what’s called an Investigational New Drug Application with the FDA.

A pharmaceutical company can’t make real money from a simple “dietary ingredient.” That’s because you can’t patent something that’s found in nature and been consumed by humans for thousands of years. However – they can create a novel formulation of a dietary ingredient, e.g. more easily absorbed, time-released, combination with another specific substance – and obtain a patent on that unique formulation.

Two years into the sale of Anatabloc, Rock Creek Pharmaceutical decided to do clinical research on the effectiveness of anatabine to relieve some to the symptoms of Alzheimer’s. They filed an “Investigational New Drug (IND) application with the FDA to get permission to carry out clinical trials.

Even though Star Scientific put it on the market as a dietary supplement a full two years before the application for the IND was made, the FDA contends that the failure to file an NDI notification (before it was sold to the public) makes this period a time it was not legally marketed. Thus, the IND application trumps Anatabloc’s earlier entry to the general public. It goes back, once again, to anatabine’s status as “present in the food supply as an article used for food in a form in which the ingredient has not been chemically altered.”

Tobacco Exclusion

But why stop there? After all the citations regarding “drug claims,” “NDI status” and “lack of notification”, the IND application trumping the fact that Anatabloc had been on the market for two years prior – the FDA then goes on to cite anatabine simply cannot be a dietary supplement because it’s a “component of tobacco.”

Anatabine is a biomolecule, a metabolite found in cauliflower, peppers, potatoes, tomatoes and yes it is also found in tobacco. Therefore to summarily dismissed anatabine as excluded from the DSHEA definition of a dietary supplement is a grand over-reach on the part of the FDA.

21 U.S. Code § 321 states:

1) The term “tobacco product” means any product made or derived from tobacco that is intended for human consumption, including any component, part, or accessory of a tobacco product (except for raw materials other than tobacco used in manufacturing a component, part, or accessory of a tobacco product).

Anatabine is not a “component or part” which by definition would be stem, leaf, flower, seed or root. As chlorophyll-a is a biomolecule in tobacco, so is anatabine – and the FDA has not prohibited the sale of chlorophyll supplements.

Congressional Members representing states where tobacco is an important agricultural crop should take heed of this. According to the interpretation used against Rock Creek Pharmaceuticals, the FDA has basically stated tobacco plants should be eradicated from the earth.

Response

On January 31, 2014 Rock Creek Pharmaceutical responded to the warning letter issued by the FDA the prior month. They contested the FDA’s position with respect to the status of the Company’s dietary supplement. On the issue of misbranding due to drug claims they pointed out the fact all text and materials objected to by the FDA in the Warning Letter had been removed from the Anatabloc website.

Although the company did not believe (and has not conceded) that the submission of an New Dietary Ingredient Notification (NDIN) was a pre-requisite to the lawful marketing of anatabine as a supplement ingredient, they voluntarily submitted an NDIN to the FDA in June 2014 for the dietary ingredient anatabine.

The FDA came back in September 2014 to state that this application was basically null and void because it still considers anatabine citrate a drug, “as it is intended to provide anti-inflammatory support, and is the subject of a previously filed Investigational New Drug Application (INDA)”

Yes, and I’m taking Omega3 fish oils for their pleasant flavor.

Conclusion

It’s time for those of us who found safe, affordable, relief from a natural product of nature to demand the FDA recognize the weakness in their argument against the dietary supplement Anatabloc.

The law states it’s incumbent upon the FDA to determine if a product under its regulatory aegis is in fact dangerous to the public. In the case of Anatabloc, the FDA failed to do that. However, through technical bureaucratic fault-finding based on invalid arguments it has financially forced the manufacturer of Anatabloc to suspend it sales. In this action, the FDA has denied the very people who it is intended to protect their right to a safe, natural cost – effective dietary supplement.